Pharmaceuticals intended for oral administration are typically provided in solid form as tablets, capsules, pills, lozenges, or granules. Tablets are swallowed whole, chewed in the mouth, or dissolved in the oral cavity. Chewable or disintegrative tablets are often employed in the administration of pharmaceuticals where it is impractical to provide a tablet for swallowing whole, for instance with pediatric patients. In addition, with chewable tablets, the act of chewing helps to break up the tablet granules as the tablet disintegrates and may increase the rate of absorption by the digestive tract.
Workers in the field continue to try to improve the flavor and mouthfeel of chewable tablets and other comestibles. For instance, U.S. Pat. No. 4,327,076 to Puglia et al. relates to a chewable tablet formed of granules of active ingredient isolated from other ingredients of the tablet by admixing those granules with granules formed of an edible fat or oil absorbed on a fat-absorbing material, such as microcrystalline cellulose. The granules are blended with one or more tablet bonders, such as dextrose monohydrate. In addition, the tablet may also comprise other conventional ingredients, such as sweeteners.
U.S. Pat. No. 4,327,077 to Puglia et al. also relates to a chewable tablet. The tablet comprises granules of a recrystallized fatty material such as chocolate, a bulking material such as sugar or an active ingredient bound up in the granules of recrystallized fatty material, and a direct compaction vehicle that may be dextrose monohydrate.
PCT Application No. WO 99/47126 discloses compressed tablets capable of rapidly dissolving in aqueous solutions, comprising at least one non-saccharide water soluble polymer such as polyvinylpyrrolidone, optionally a saccharide of low moldability such as glucose, optionally a saccharide of high moldability such as maltose, sorbitol or a mixture thereof, and optionally a sweetener such as sucralose. These tablets are prepared by wet granulation, specifically a) granulating a formulation comprising the non-saccharide, water soluble polymer and active ingredient using no organic solvents, (b) compressing this into tablet form, (c) humidifying the tablet by exposing it to an aerated environment having at least about 50 to 100% relative humidity, and (d) drying the tablet.
Chewable tablets are known. U.S. Pat. No. 5,489,436 describes a chewable tablet made from a coated medicament wherein the coating comprises a mixture of dimethylaminoethyl methacrylate, a neutral methacrylic acid ester and a cellulose ester. The coating is described as a reverse enteric coating, which is not water soluble in non-acidic conditions but is soluble in acidic conditions. U.S. Pat. No. 4,851,226 describes a chewable medicament tablet made from coated granules of medicament wherein the coating on said granules comprises a blend of cellulose acetate or cellulose acetate butyrate and polyvinyl pyrrolidone. U.S. Pat. No. 4,800,087 describes a microencapsulating polymer for coating a pharmaceutical core that is capable of taste-masking the active compound. The polymer is described as maintaining its integrity when tabletted and/or chewed and can provide immediate release of the active compound in the stomach, or can release the active ingredient in the upper intestinal tract or in a sustained release fashion. U.S. Pat. No. 4,970,081 describes rapidly disintegrating aspirin tablets wherein the aspirin granules have been coated to provide a zero order release of the active ingredient.
It is also known that pharmaceutically active ingredients can be provided with enteric coatings. Providing enteric coatings on the active ingredient for aspirin, however, presents a number of unique challenges due to potential hydrolysis of the active to produce free salicylic acid. Several patents have been published that allegedly describe stabilized enteric-coated aspirin compositions, such as U.S. Pat. No. 4,900,559, which describes a stabilized enteric coated aspirin granules product prepared by commingling the enteric coated aspirin granule with glutamic acid hydrochloride. U.S. Pat. No. 5,068,110 allegedly improves the stability of an enteric-coated dosage form through the application of higher levels of coatings or by the application of higher levels of coatings in combination with the use of a protective coating.
Acid-labile actives, enteric coated and non-enteric coated, have been formulated as orally disintegratable tablets. For example, published PCT application WO 03/007917 describes a dosage form for enteric coated proton pump inhibitors in the form of a multi-particulate tablet that disintegrates in the mouth. Published U.S. Patent application 2004/0110661 describes a rapidly disintegrating tablet for acid-labile active ingredients. The tablet is described as comprising a plurality of individual active ingredient units together with excipients, wherein the acid-labile active is present in individual active ingredient units in a matrix composed of a mixture of a solid paraffin and one or more of a fatty alcohol, triglycerides and fatty acid ester. Published U.S. Patent application 2002/0142034 describe an orally disintegrable tablet that comprises fine granules having an average granule diameter of 400 μm or less.
There remains a need for a pharmaceutical product that can be chewed or that disintegrates in the mouth, which contains an enteric-coated aspirin active ingredient.